MSA (multiplication stimulating activity) has been found to be elevated in fetal rat serum. The MSA is exclusively bound to an albumin sized binding protein. In fetal rat serum; the larger, gammaglobulin sized, growth hormone dependent binding protein is absent. Experiments utilizing anti-insulin receptor antibody have demonstrated that the weak insulinlike activity of MSA (and probably other somatomedins in rat adipocytes) is due to cross-reaction of MSA with the insulin receptor. The antiinsulin receptor Fab blocked the stimulation of glucose oxidation by MSA in the rat adipocytes while only minimally inhibiting binding of MSA to its own receptor. MSA was found to stimulate proteoglycan synthesis as measured by 35S-sulfate incorporation in swarm rat chondrosarcoma chondrocytes in monolayer culture. Surprisingly, insulin also stimulated proteoglycan synthesis at physiologic concentrations. Experiments with anti-insulin receptor antibody demonstrated that insulin's biological effect was mediated via the insulin receptor rather than via somatomedin receptors.